1. Field of the Invention
The present invention relates to a process for producing o-sulfobenzimide (1.2-benzoisothiazole-3-on-1.1-dioxide) which is useful as a medicinal agent (sweetener for diabetics), as food additives (sweetener) and as intermediates for agricultural chemicals in high yield by using a methylbenzoate-o-sulfonate which is easily obtained from o-chlorobenzoic acid by unique reaction steps.
2. Description of the Prior Art
In the past, 1.2-benzoisothiazole-3-on-1.1-dioxide having the formula: ##STR3## has been produced by the following sequence of reaction steps shown in Reaction scheme (I) in which: (1) toluene is chlorosulfonated; (2) o-toluenesulfochloride and p-toluenesulfochloride produced in the first step are separated and purified; (3) o-toluenesulfochloride separated and purified in the second step is reacted with ammonia; and (4) o-toluenesulfonamide produced in the third step is oxidized with a solution of bichromate in conc sulfuric acid. (J. Am. Chem. Soc., 1, page 426, 1879; BP No. 174,913 and BP No. 682,800) ##STR4##
1.2-Benzoisothiazole-3-on-1.1-dioxide has also been produced by the reaction sequence shown in Reaction scheme (2), in which: (1) phthalic anhydride is reacted with ammonia; (2) phthalimide produced in the first step is subjected to the Hoffmann reaction; (3) o-aminobenzoic acid produced in the second step is diazotized; (4) sodium sulfide is reacted with the diazobenzoic acid produced in the third step; (5) sodium dithiodibenzoate produced in the fourth step is treated with an acid; (6) dithiodibenzoic acid produced in the fifth step is methyl esterified; (7) dimethyl dithiodibenzoate produced in the sixth step is reacted with chlorine; and (8) methyl o-sulfochlorobenzoate produced in the seventh step is reacted with ammonia. (Chemical Engineering, Vol. 61, No. 7, page 128, 1954). ##STR5##
In the conventional process of Reaction scheme (1) large amounts of p-toluene-sulfochloride are produced from toluene as by-product together with o-toluenesulfochloride in the first step. Accordingly, the separation and purification procedures of the second step are quite troublesome. That is, the reaction mixture formed in the first step is poured into water to precipitate crystals of p-toluenesulfochloride and the crystals are centrifugally separated. The oily product of o-toluenesulfochloride which remains is further cooled to precipitate crystals of p-toluenesulfochloride, and the operation is repeated. However, it is difficult to separate all of the p-toluenesulfochloride from the oily o-toluenesulfochloride. Because of these difficulties, it is necessary to separate p-toluenesulfonamide as a by-product after the reaction with ammonia in the third step. In the fourth step of the reaction sequences it is necessary to treat a large amount of the waste acid from the bichromate and conc. sulfuric acid oxidation solution used in the fourth step. The process is also complicated by the necessity of using a large electrolyzer in the recovery and reuse of the chromium oxide formed as the reduced product from the bichromate oxidant. Moreover, a serious disadvantage of the conventional process is the fact that both o-toluenesulfonamide and p-toluenesulfonamide are believed to cause cancer. Because these materials are produced in the conventional process, it is necessary to separate the toxic compounds to purify the product. If the toxic compounds remain with 1.2-benzoisothiazole-3-on-1.1-dioxide in the use of the same as a food additive, there is the possibility of adverse affects on the human body. Accordingly, the conventional process is not a hygienically safe process.
In the conventional process of Reaction scheme (2) phthalic anhydride is used as the starting material, and it is necessary to use an eight step reaction sequence. Accordingly, the operation is complicated and it is difficult to attain high yields of 1.2-benzoisothiazole-3-on-1.1-dioxide such as about 50% based on the phthalic anhydride starting material. These processes are not satisfactory as industrial methods.